Effect of carbonic anhydrase inhibition on proximal tubular bicarbonate reabsorption

Clapp, James R.; Watson, John F.; Berliner, Robert W.

doi:10.1152/ajplegacy.1963.205.4.693

Cited by 41 publications

(16 citation statements)

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“…The proximal tubule, therefore, unlike the distal tubule, does not demonstrate a reciprocal relationship between hydrogen and potassium ion secretion. These results confirm similar observations made in rodents (2,16).…”

Section: Discussionsupporting

confidence: 93%

Potassium reabsorption in the proximal tubule of the dog nephron.

Watson¹

1966

J. Clin. Invest.

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Previous micropuncture studies ( 1,2) have demonstrated that potassium is extensively reabsorbed in the proximal tubule under conditions in which the net excretion of potassium in th-e urine varies, supporting the hypothesis that major adjustments in the rate of potassium excretion occur in distal parts of the nephron (3). To further evaluate the reabsorptive process in the dog nephron, fractional reabsorption of potassium from the proximal tubule was studied by micropuncture techniques during reductions in glomerular filtration rate (GFR) produced by renal arterial constriction, during proximal tubular inhibition of sodium reabsorption produced by isotonic saline infusion (4, 5), and during stimulation of potassium secretion by potassium loading and acetazolamide administration. MethodsMale and female mongrel dogs weighing between 9 and 18 kg were used as experimental animals. The dogs were anesthetized by the rapid injection of 200 mg of thiopental sodium administered intravenously as a 2.5% solution in distilled water; small additional doses were administered from time to time to maintain the desired level of anesthesia. Indwelling catheters were inserted into the ureters through a suprapubic midline incision. Polyethylene catheters were also inserted into the foreleg veins and the femoral vein or artery for the administration of fluids and collection of blood. The left kidney (experimental) was exposed through a flank incision and prepared for micropuncture as previously reported (6). Methods of tubular fluid collection and identification were also similar to those previously reported (6).In all experiments, 15-minute urine collection periods for the determination of inulin and potassium clearances * Submitted for publication December 9, 1965; accepted May 18, 1966. Supported by grant AM-07352-03 from the National were obtained while tubular fluid samples were being collected. After appropriate priming and sustaining infusions of inulin had been given, 30 minutes was allowed to elapse before collections were begun to insure stable concentrations of inulin in plasma. Venous or arterial blood was drawn at the midpoint of each period, and urine was collected through the ureteral catheters.Four groups of dogs were studied: 1) normal hydropenia, 2) hydropenia with renal arterial constriction, 3) potassium loaded with acetazolamide administration, and 4) normal dogs undergoing isotonic saline diuresis. In the hydropenic group with renal arterial constriction, an adjustable rubber clamp was placed around the renal artery of the experimental kidney before its bifurcation. The renal artery was gradually constricted until there was an observable decrease in kidney tissue turgor, and urine flow was reduced by at least 50% as compared with the control kidney. Only those tubular fluid samples were used that were collected during clearance periods in which the GFR of the experimental kidney was 75%o or less of the control kidney.Potassium-loaded animals were fed a diet containing 20 g of KCI daily for 1 week before the ...

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Section: Discussionsupporting

confidence: 93%

Potassium reabsorption in the proximal tubule of the dog nephron.

Watson¹

1966

J. Clin. Invest.

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“…Strong support for this assumption was given by Pitts and Lotspeich11 and Rector et al 16 However, Clapp et al12 opposed these opinions, who found the Diamox-inhibition in the whole nephron, especially, in the proximal tubules. This was reconfirmed by Rector et al17 In brief, the findings in this study favor the opinion of Clapp et al 12 Principal point of my results is that the CAH activity is most concentrated in the proximal tubules, while the distal tubules show a moderate, but far less concentrated amount of CAH. The specificity of the histochemical technique used here may be supported by the completely negative reaction in the sections treated with the substrate medium containing a small amount of Diamox.…”

Section: Discussionsupporting

confidence: 90%

Histochemical Study of Carbonic Anhydrase in the Kidney of Mouse, with Special Reference to the Inhibitory Effect of Diamox

Ishizaki¹

1969

Tohoku J. Exp. Med.

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“…This postulation is supported by the data of Agus and co-workers (6,7) in micropuncture experiments that both PTH and its cellular messenger, cyclic AMP, inhibit proximal tubular reabsorption of phosphate, sodium, and water. Inhibition of carbonic anhydrase by pharmacological agents, such as acetazolamide, also inhibits proximal tubular reabsorption of phosphate, sodium, and water (8)(9)(10)(11) as well as bicarbonate (12)(13)(14)(15)(16)(17). The qualitative similarity between the inhibition of proximal tubular reabsorption of those ions after the PTH administration and that after the inhibition of carbonic anhydrase by acetazolamide suggests that at least a part of renal effect of PTH is mediated through the inhibition of carbonic anhydrase in proximal tubules.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of carbonic anhydrase by parathyroid hormone and cyclic AMP in rat renal cortex in vitro.

Beck¹,

Kim²,

Wolak³

et al. 1975

J. Clin. Invest.

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A B S T R A C T It has been demonstrated that parathyroid hormone (PTH) inhibits the proximal tubular reabsorption of bicarbonate, and increases the urinary excretion of that ion. There is also a qualitative similarity between the alterations of the proximal tubular reabsorption of phosphate, sodium, and water after PTH administration and after acetazolamide administration. These findings suggest that the renal effect of PTH is possibly mediated through the inhibition of carbonic anhydrase in proximal tubules. Therefore, a possible inhibitory effect of PTH on carbonic anhydrase was evaluated in the homogenate of rat renal cortex by an indicator titration method.Incubation of cortical homogenates with PTH for 10 min at 370C inhibited carbonic anhydrase activity. The inhibitory effect of PTH was ATP-, Mg"+-, and K+-dependent and temperature-dependent; inactivation of PTH by heating at 100'C abolished the effect of PTH both to activate adenylate cyclase and to inhibit carbonic anhydrase. Calcium 5 mM also partially abolished effects of PTH to activate adenylate cyclase and to inhibit carbonic anhydrase. The inhibitory effect of PTH on carbonic anhydrase was specific to renal cortex.Cyclic AMP, the intracellular messenger substance for PTH, also inhibited carbonic anhydrase in renal cortex. The cyclic AMP-induced inhibition was also Mg"+ dependent and temperature dependent, and required preincubation at 370C. But 5'-AMP, a metabolic derivative of cyclic AMP without its biological effect, had no inhibitory effect on carbonic anhydrase.All the above results are consistent with the hypothesis that PTH inhibits proximal tubular reabsorption of bicarbonate and phosphate through the inhibition of

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Effect of carbonic anhydrase inhibition on proximal tubular bicarbonate reabsorption

Cited by 41 publications

References 0 publications

Potassium reabsorption in the proximal tubule of the dog nephron.

Potassium reabsorption in the proximal tubule of the dog nephron.

Histochemical Study of Carbonic Anhydrase in the Kidney of Mouse, with Special Reference to the Inhibitory Effect of Diamox

Inhibition of carbonic anhydrase by parathyroid hormone and cyclic AMP in rat renal cortex in vitro.

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